Biocements
Particularly within orthopaedics, there is a need for biomaterials that can be finished for final use in a clinical environment, i.e. compounds which can be finally shaped at the time of a surgical operation. After shaping, the material should harden, or cure either uncovered in the operating theatre or positioned in the body. There is no generally accepted name for this type of materials. The concept of bone cement generally applies to the established polymer based cements often used for the fixation of hip-implants in the femoral bone. Biocement is a more general word for workable biocompatible materials, which cure in-situ through chemical reactions, including the ceramic compounds, further described below.
PMMA Bone Cements
There is a number of commercially available orthopaedic cements. The most established are based on the polymer polymethylmethacrylate (PMMA). This group of bone cements is mainly used for anchoring hip-joint protheses in the femoral and pelvic bones, or for the corresponding anchoring of knee joints. A big brand name among PMMA bone cements is Palacos® from Merck.
PMMA based materials have penetrated into orthopaedics, mainly due to suitable mechanical properties, a high degree of workability before curing, and a practical curing time.
The mechanical properties of PMMA bone cements are characterised by a relatively high fracture toughness, a compressive strength (80–120 MPa) being equal to or slightly lower than that of a femoral bone (130–200 MPa), and a considerably lower elastic modulus than the latter; 1–3 GPa for the cement compared to 10–15 GPa for the femoral bone, see Table 1.
However, PMMA-based cements have poor biocompatibility. Tissue in-growth cannot be established. Since the polymerisation does not proceed to completion, the material tends to leak monomers, a component of recognised toxic character. Furthermore, during curing heat development is such that the temperature rises to levels (above 50° C.) that cause cell necrosis in adjacent tissues.
A further disadvantage with PMMA-based cements is the shrinkage that occurs during curing (approximately 2–5%). This impairs the mechanical anchoring in the adjacent bone and consequently the possibility of early loading of the fracture. Preferably, orthopaedic cements should expand slightly during curing, as will be discussed further below.
Ceramic Biocements
In addition to the polymer based bone cements, there is a number of chemically curing cements based on ceramic components. Ceramic biocements for orthopaedic applications are often based on calcium phosphate, calcium carbonate or calcium sulphate. Examples of ceramic biocements products are: Norian SRS®, Osteoset®, Proosteon® and Biobon®.
In general, ceramic cements are much more biocompatible than those of PMMA. However, they suffer from insufficient mechanical strength. The manufacturers of Norian® and Biobon® provide compressive strength values around 30 and 40 MPa, respectively, see e.g. Table 1, much lower values that for natural bone.
Norian SRS is described in “Norian SRS versus external fixation in redisplaced distal radial fractures—A randomized study in 40 patients”, by P. Kopylov, K. Runnqvist, K. Jonsson and P. Aspenberg, Acta Orthop Scand, 1999; 70 (1) 1–5.
Information about Biobon is given in “Resorbable calcium phosphate bone substitute”, by Knaack D, Goad M E P, Aiolova M, Rey Ch, Tofighi A, Chakravarthy P, Lee D D, J Biomed Mater Res (Applied Biomater) 1998; 43: 399–409.
Other Biomaterials
As for ceramics materials, special attention has been paid to various types of hydroxyapatites (or calcium phosphates), against which bone tissue regenerates excellently. Hydroxyapatites are also naturally occurring in bone tissue. The mineral part (bone contains about 68–70% of minerals) is mainly calcium phosphates substances, e.g. hydroxyapatite, Ca10(PO4)6(OH)2. Bone attachment to hydroxyapatite is described in B. Sandén, C. Olerud, S. Larsson, “Hydroxyapatite coating enhances fixation of loaded pedicle screws: a mechanical in vivo study in sheep”, Eur Spine J (2001) 10: 334–339).
Hydroxyapatite and other calcium phosphates have too poor mechanical properties for dental and orthopaedic applications when used alone (see WO/11979).
Another, less spread biomaterial is calcium aluminate, a central component of the present invention. Calcium aluminate for medical applications is described e.g. in S. F. Hulbert, F. A. Young, R. S. Mathews, J. J. Klawitter, C. D. Talbert and F. H. Stelling, “Potential of Ceramic Materials as Permanently Implantable Skeleton Prostheses”, J. Biomed. Mater.res, vol. 4, PP. 433–456 (1970).
Calcium aluminate has been explored as a tooth filling material, e.g. the product Doxadent® produced by Doxa Certex A B, see e.g. PCT/SE99/01729, “Sätt att framställa en kemiskt bunden keramisk produkt, samt produkt”, 29 Sep. 1999; and PCT/SE99/01803, “Dimension stable binding agent systems”, 08 Oct. 1999.
SE-463 493 discloses a chemically bound ceramic material comprising a first binding agent selected from the group comprising aluminates, silicates and phosphates. The material is achieved through a specified production technique involving pre-compaction of the ceramic body. In addition, the ceramic material may comprise an inert phase of hydroxyapatite or oxides of titanium, zirconium, zinc and aluminium. The reasons for these additives are strength and biocompatibility.